Safety, Tolerability, and PK of AN2728 in Adolescents With Atopic Dermatitis

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Number of Participants With Local Tolerability Symptoms According to Severity on Baseline [ Time Frame: Baseline ]

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Baseline were reported in this outcome measure.

Number of Participants With Local Tolerability Symptoms According to Severity on Day 2 [ Time Frame: Day 2 ]

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 2 were reported in this outcome measure.

Number of Participants With Local Tolerability Symptoms According to Severity on Day 4 [ Time Frame: Day 4 ]

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 4 were reported in this outcome measure.

Number of Participants With Local Tolerability Symptoms According to Severity on Day 6 [ Time Frame: Day 6 ]

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 6 were reported in this outcome measure.

Number of Participants With Local Tolerability Symptoms According to Severity on Day 8 [ Time Frame: Day 8 ]

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 8 were reported in this outcome measure.

Number of Participants With Local Tolerability Symptoms According to Severity on Day 9 [ Time Frame: Day 9 ]

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 9 were reported in this outcome measure.

Number of Participants With Local Tolerability Symptoms According to Severity on Day 15 [ Time Frame: Day 15 ]

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 15 were reported in this outcome measure.

Number of Participants With Local Tolerability Symptoms According to Severity on Day 22 [ Time Frame: Day 22 ]

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 22 were reported in this outcome measure.

Number of Participants With Local Tolerability Symptoms According to Severity on Day 29 [ Time Frame: Day 29 ]

Local tolerability symptoms, burning or stinging, were classified according to severity as: 1) none = no stinging or burning, 2) mild = slight warm, tingling sensation; not really troublesome, 3) moderate = definite warm; tingling or stinging sensation; troublesome and 4) severe = hot, tingling or stinging sensation that caused definite discomfort. Number of participants with local tolerability symptoms according to severity on Day 29 were reported in this outcome measure.

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline (Day 1) up to Day 29 ]

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death;initial or prolonged inpatient hospitalization; life- threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Day 29 that were absent before treatment or that worsened relative to pretreatment state.

Number of Participants With Clinically Significant Vital Signs Abnormalities [ Time Frame: Baseline (Day 1) up to Day 29 ]

Vital signs (temperature, respiratory rate, pulse, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes. Clinical significance of vital signs was determined at the investigator's discretion.

Number of Participants With Clinically Significant Laboratory Test Abnormalities [ Time Frame: Baseline (Day 1) up to Day 29 ]

Time to reach maximum plasma concentration of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 1 was reported in the outcome measure.

Area Under the Concentration-Time Curve From Hour Zero To the 12 Hour Post-Dose Measurable Concentration of AN2728 and Major Oxidative Metabolites of AN2728: Day 1 [ Time Frame: Pre-dose (0 hour), 1, 2, 4, 6, 8 and 12 hours post-dose on Day 1 ]

Area under the concentration-time curve from hour zero to the 12 hour post-dose measurable concentration, of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 1 was reported in the outcome measure.

Apparent terminal half-life, of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 1 was reported in the outcome measure. Apparent terminal half-life is the time measured for the drug concentration to decrease by one-half in plasma.

Time to reach maximum plasma concentration of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 8 was reported in the outcome measure.

Area Under the Concentration-Time Curve From Hour Zero To the 12 Hour Post-Dose Measurable Concentration of AN2728 and Major Oxidative Metabolites of AN2728: Day 8 [ Time Frame: Pre-dose (0 hour), 1, 2, 4, 6, 8 and 12 hours post-dose on Day 8 ]

Area under the concentration-time curve from hour zero to the 12 hour post-dose measurable concentration, of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 8 was reported in the outcome measure.

Apparent terminal half-life, of AN2728 and its two identified oxidative metabolites, AN7602 and AN8323 on Day 8 was reported in the outcome measure. Apparent terminal half-life is the time measured for the drug concentration to decrease by one-half in plasma.

Secondary Outcome Measures
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Number of Participants Who Achieved Treatment Success Based on Investigator's Static Global Assessment (ISGA) [ Time Frame: Baseline up to Day 29 ]

ISGA assess severity of atopic dermatitis on a 5 point scale ranged from 0 (clear) to 4 (maximum severe), where higher scores indicate higher degree of atopic dermatitis. Grades for classification of severity: 0= clear (minor residual discoloration, no erythema or induration or papulation, no oozing or crusting), 1= almost clear (trace faint pink erythema, with barely perceptible induration or papulation and no oozing or crusting), 2= mild (faint pink erythema with mild induration or papulation and no oozing or crusting), 3= moderate (pink-red erythema with moderate induration or papulation with or without oozing or crusting) and 4= severe (deep or bright red erythema with severe induration or papulation and with oozing or crusting). Treatment success was defined as ISGA score of 0 or 1, and a minimum improvement of 2 grades in ISGA from Baseline to Day 29.

Change From Baseline in Signs and Symptoms of Atopic Dermatitis at Day 8, 15, 22 and 29 [ Time Frame: Baseline, Day 8, 15, 22, 29 ]

5 signs and symptoms of atopic dermatitis were: 1) erythema, 2) pruritus, 3) exudation, 4) excoriation and 5) lichenification. The severity of each of these 5 signs and symptoms were assessed on a 4 point scale, ranging from 0 (none) to 3 (severe). Higher scores (for each of the 5 signs and symptoms) indicate higher degree of severity of atopic dermatitis.

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Ages Eligible for Study:

12 Years to 17 Years (Child)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Male or female 12 to 17 years of age, inclusive

Clinical diagnosis of atopic dermatitis (according to the criteria of Hanifin and Rajka)

Have adequate venous access to permit repeated PK sampling on Days 1 - 9 through uninfected skin that has not been treated with study drug; each untreated venous access area should provide a margin of at least 5 cm radius around the venipuncture site

Willing and able to comply with study instructions and commit to attending all visits

Females must use a highly effective method of birth control.

Parent/guardian has the ability to understand, agree to and sign the study Informed Consent Form (ICF) prior to initiation of any protocol-related procedures; subject has the ability to give assent

Exclusion Criteria:

Significant confounding conditions as assessed by study doctor

Unstable or actively infected AD

Active or potentially recurrent dermatologic condition other than atopic dermatitis that may confound evaluation

Concurrent or recent use of certain topical or systemic medications or phototherapy without a sufficient washout period

Treatment for any type of cancer (except squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ of the skin, curatively treated with cryosurgery or surgical excision only) within the last 5 years

Current pregnancy or lactation, or intent to become pregnant during the study

Known sensitivity to any of the components of the study drug

Participated in any other trial of an investigational drug or device within 30 days or participation in a research study concurrent with this study